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Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 23(11)
- Publication Year :
- 2003
-
Abstract
- Opiate abuse causes adaptive changes in several processes of synaptic transmission in which the glutamatergic system appears a critical element involved in opiate tolerance and dependence, but the underlying mechanisms remain unclear. In the present study, we found that glutamate uptake in hippocampal synaptosomes was significantly increased (by 70% in chronic morphine-treated rats) during the morphine withdrawal period, likely attributable to an increase in the number of functional glutamate transporters. Immunoblot analysis showed that expression of GLT1 (glutamate transporter subtype 1) was identified to be upregulated in synaptosomes but not in total tissues, suggesting a redistribution of glutamate transporter expression. Moreover, the increase in glutamate uptake was reproduced in cultured neurons during morphine withdrawal, and the increase of uptake in neurons could be blocked by dihydrokainate, a specific inhibitor of GLT1. Cell surface biotinylation and immunoblot analysis showed that morphine withdrawal produced an increase in GLT1 expression rather than EAAC1 (excitatory amino acids carrier 1), a neuronal subtype, at the cultured neuronal cell surface, whereas no significant change was observed in that of cultured astrocytes. Electron microscopy also revealed that GLT1 expression was markedly increased in the nerve terminals of hippocampus and associated with the plasma membranein vivo. These results suggest that GLT1 in hippocampal neurons can be induced to translocate to the nerve terminals and express on the cell surface during morphine withdrawal. The translocation of GLT1 at synapses during morphine withdrawal provides a neuronal mechanism for modulation of excitatory neurotransmission during opiate abuse.
- Subjects :
- Male
medicine.medical_specialty
Amino Acid Transport System X-AG
Excitatory Amino Acid Transporter 3
Presynaptic Terminals
Glutamic Acid
Behavioral/Systems/Cognitive
Neurotransmission
Hippocampal formation
Glutamate Plasma Membrane Transport Proteins
Biology
Hippocampus
Rats, Sprague-Dawley
Glutamatergic
Internal medicine
medicine
Animals
RNA, Messenger
Cells, Cultured
Neurons
Morphine
Symporters
General Neuroscience
Long-term potentiation
Rats
Substance Withdrawal Syndrome
Up-Regulation
Protein Transport
Endocrinology
Excitatory Amino Acid Transporter 2
Astrocytes
Synapses
Excitatory postsynaptic potential
Opiate
Neuroscience
Morphine Dependence
Synaptosomes
Subjects
Details
- ISSN :
- 15292401
- Volume :
- 23
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....ad6db7ef8e7eb90270e8516b2dd66d71